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PTPN11 Knockdown Prevents Changes in the Expression of Genes Controlling Cell Cycle, Chemotherapy Resistance, and Oncogene-Induced Senescence in Human Thyroid Cells Overexpressing BRAF V600E Oncogenic Protein

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dc.contributor.author Putlyaeva L.V.
dc.contributor.author Demin D.E.
dc.contributor.author Uvarova A.N.
dc.contributor.author Zinevich L.S.
dc.contributor.author Prokofjeva M.M.
dc.contributor.author Gazizova G.R.
dc.contributor.author Shagimardanova E.I.
dc.contributor.author Schwartz A.M.
dc.date.accessioned 2021-02-24T20:31:55Z
dc.date.available 2021-02-24T20:31:55Z
dc.date.issued 2020
dc.identifier.issn 0006-2979
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/160735
dc.description.abstract © 2020, Pleiades Publishing, Ltd. The MAPK (RAS/BRAF/MEK/ERK) signaling pathway is a kinase cascade involved in the regulation of cell proliferation, differentiation, and survival in response to external stimuli. The V600E mutation in the BRAF gene has been detected in various tumors, resulting in a 500-fold increase in BRAF kinase activity. However, monotherapy with selective BRAF V600E inhibitors often leads to reactivation of MAPK signaling cascade and emergence of drug resistance. Therefore, new targets are being developed for the inhibition of components of the aberrantly activated cascade. It was recently discovered that resistance to BRAF V600E inhibitors may be associated with the activity of the tyrosine phosphatase SHP-2 encoded by the PTPN11 gene. In this paper, we analyzed transcriptional effects of PTPN11 gene knockdown and selective suppression of BRAF V600E in a model of thyroid follicular epithelium. We found that the siRNA-mediated knockdown of PTPN11 after vemurafenib treatment prevented an increase in the expression CCNA1 and NOTCH4 genes involved in the formation of drug resistance of tumors. On the other hand, downregulation of PTPN11 expression blocked the transcriptional activation of genes (p21, pl5, pl6, RBI, and IGFBP7) involved in cell cycle regulation and oncogene-induced senescence in response to BRAF V600E expression. Therefore, it can be assumed that SHP-2 participates not only in emergence of drug resistance in cancer cells, but also in oncogene-induced cell senescence.
dc.relation.ispartofseries Biochemistry (Moscow)
dc.subject BRAFV600E
dc.subject oncogene-induced senescence
dc.subject SHP-2
dc.subject thyroid tumor
dc.title PTPN11 Knockdown Prevents Changes in the Expression of Genes Controlling Cell Cycle, Chemotherapy Resistance, and Oncogene-Induced Senescence in Human Thyroid Cells Overexpressing BRAF V600E Oncogenic Protein
dc.type Article
dc.relation.ispartofseries-issue 1
dc.relation.ispartofseries-volume 85
dc.collection Публикации сотрудников КФУ
dc.relation.startpage 108
dc.source.id SCOPUS00062979-2020-85-1-SID85079126230


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  • Публикации сотрудников КФУ Scopus [22633]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

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